Transgenic models of human disease are valuable tools to study etiologies of tumorigenesis as well as to serve as in vivo systems to test various therapeutic approaches. We have developed transgenic mice which develop prostate cancer in males and mammary cancer in females. These transgenic mice carry a chimeric gene in which the early region of simian virus (SV)40 T-antigen (Tag) is expressed under the regulatory control of the rat hormone-responsive C3(1) gene. These animals develop adenocarcinomas several months after the onset of dysplastic lesions in the target tissues. Therefore, we believe that these transgenic mice may serve as a useful model to study multistep tumorigenesis of prostate and mammary adenocarcinoma. Tag impairs the functions of two known tumor suppressor genes, p53 and Rb, and therefore, this transgenic model may mimic mechanisms of tumorigenesis which are very relevant to the human situation. The roles of p53 as well as other antioncogenes, oncogenes and growth factors implicated in the development of prostate and mammary cancer are being extensively investigated using this transgenic model. We have determined that prostate and mammary tumorigenesis in these mice is hormone-responsive. Cell lines have been established from both the transgenic prostate and mammary tumors and are being characterized. Polymerase chain reaction (PCR) differential display and two-dimensional protein gel electrophoresis are being used to identify genes which may be involved in the multistep process of tumorigenesis. This transgenic model is also being used to test various chemopreventative as well as standard therapeutic agents for prostate and mammary cancers.